DESCRIPTION (provided by investigator): Project Summary/Abstract Exposure of humans to secondhand smoke (SHS) is associated with adverse health effects including cancer, respiratory disease, and cardiovascular disease. The increasing body of evidence linking SHS exposure to increased risk of morbidity and mortality has led to passage of indoor smoking bans. However, as smoking bans are implemented in restaurants, bars, and other public indoor establishments, smokers move outdoors and an increasing number of non-smokers are exposed to outdoor SHS. While the public's concern is justifiable, human health risk assessment and policy making are impeded by the lack of empirical data on outdoor SHS levels and health outcomes attributable to SHS commonly encountered outdoors. The primary objectives of this application are to conduct systematic exposure and acute health endpoint assessments using environmental markers of tobacco smoke, biomarkers of tobacco smoke exposure, and biomarkers of acute oxidative stress and pulmonary injury. Preliminary work has shown significant positive correlations between particulate matter (PM2.5) and/or carbon monoxide (CO) and number of smokers outside establishments, significant increases in salivary cotinine, and measurable increases in urinary 4-(N- methylnitrosamino)-1-(s-pyridyl)-1-butanol (NNAL) in subjects exposed to SHS outside restaurants and bars. We hypothesize that a dose-dependent increase in biomarkers of tobacco smoke, cotinine and NNAL, in subjects exposed to SHS outside restaurants and bars;higher concentrations of cotinine and NNAL will be measured in subjects outside bars compared to subjects outside restaurants due to higher number of smokers outside the bars. We also hypothesize that subjects exposed to SHS will have a dose-dependent increase in 8-isoprostane, a measure of oxidative stress, as well as a transient increase in serum Clara cell protein (CC16), a marker of altered lung epithelial permeability, after exposure to outdoor SHS. To test these hypotheses, we plan to conduct human exposures to SHS originating from regular smokers outside of restaurants and bars in downtown Athens, Georgia. Exposures will be characterized using real-time area PM2.5 and CO monitors, time-integrated passive area nicotine monitors, as well as biological markers, salivary cotinine and urinary NNAL. Acute health endpoints will be determined by measuring urinary 8-isoprostane, a product of lipid peroxidation and validated oxidative stress biomarker, as well as serum CC16 to assess oxidative damage to the lung epithelium. This proposed study seeks to provide relevant data on outdoor SHS exposure and associated acute health outcomes that may be used for human health risk assessment and policy making. PUBLIC HEALTH RELEVANCE: In the setting of bars and restaurants where indoor smoking is banned and outdoor smoking areas are available, the primary objectives of this applications are to conduct systematic exposure and acute health endpoint assessments in non-smokers using environmental markers of SHS exposure, biomarkers of SHS exposure, and biomarkers of acute oxidative stress and pulmonary injury. These data are important for human health risk assessment and policy making relevant to SHS exposures in these outdoor settings - an area of growing public health concern.